A significant portion of the NH4 + secreted by the proximal tubule is reabsorbed by the loop of Henle. The TAL is the primary site of this NH4 + reabsorption, with NH4 + substituting for K+ on the 1Na+/1K+/2Cl− symporter. In addition the lumen-positive transepithelial voltage in this segment drives paracellular reabsorption of NH4 + .
678 SECTION7Berne & Levy Physiology •Fig. 37.6 GeneralschemeforexcretionofH+withnon-HCO3−urinarybuffers(titratableacid).Theprimaryurinarybufferisphosphate(HPO42−).AH+-secretingintercalatedcellisshown.Forsimplicity,onlytheH+-ATPaseisdepicted.H+secretionbytheH+,K+-ATPasealsotitratesluminalbuffers.ATP,adenosinetriphosphate;CA,carbonicanhydrase.Tubular fluid Blood Cl– CO2 + H2O Buffer + H+ H-Buffer H˜ATP CA HCO3 – HCO3 –
The NH4 + reabsorbed by the TAL of the loop of Henle accumulates in the medullary interstitium. From there it is then secreted into the tubular fluid by the collecting duct.
The cells of the collecting duct express two NH3 membrane transporters known as Rhesus (Rh) glycoproteins (RhBG and RhCG).
RhBG is present in the basolateral membrane of H+-secreting intercalated cells and principal cells, and RhCG is present in both the apical and basolateral membranes of these cells. As depicted in
Fig. 37.7 , NH3 is transported across the collecting duct, a process traditionally termed nonionic diffusion. The secreted NH3 is protonated in the tubule lumen as a result of intercalated H+ secretion. Because the apical membrane has a low permeability to NH4 + it is effectively trapped in the tubular lumen, a process traditionally termed diffusion trapping.
H+ secretion by the collecting duct is critical for excretion of NH4 + . If collecting duct H+ secretion is inhibited, the NH4 + reabsorbed by the TAL of Henle’s loop will not be excreted in the urine. Instead it will be returned to the systemic circulation, where as described previously, it will be converted to urea by the liver and consume HCO3 − in the process. Thus new HCO3 − is produced during the metabolism of glutamine by cells of the proximal tubule. However, the overall process is not complete until the NH4 + is excreted (i.e., production of urea from NH4 + by the liver is prevented). Thus NH4 + excretion in urine can be used as a marker of glutamine metabolism in the proximal tubule.
AssessingNH4+ excretionbythekidneysisdoneindirectlybecauseassaysofurineNH4+ arenotroutinelyavailable.Considerforexamplethesituationofmetabolicacidosis,whereintheappropriaterenalresponseistoincreasenetacidexcretion.Accordingly,littleornoHCO3− willappearinurine,urinewillbeacidic,andNH4+ excretionwillbeincreased.Toassessthis,andespeciallytheamountofNH4+ excreted,the“urinarynetcharge”or“urineaniongap”canbecalculatedbymeasuringurinaryconcentrationsofNa+ ,K+ ,andCl−: